Experiments in this proposal are designed to improve our understanding of the control of cellular proliferation during retinal development. The first goal is to evaluate retinal progenitors and their environment in mice lacking the Chxl0 gene in order to determine how this protein facilitates proliferation in cells. Chxl0 is critically involved in normal development, and mutations in the human CHXIO gene can cause microphthalmia. The second goal is to identify factors that act cooperatively with Chxl0 to regulate cell cycle progression, since these factors are likely to be crucial regulators of retinal cell number. This will be achieved through proliferation assays and RNA and protein analysis. The final goal is to investigate the mechanisms of negative control of retinal proliferation, through analysis of the proteins mediating TGF-beta signaling. Better understanding of proliferation control through the experiments in each of these goals will help explain microphthalmias and retinal tumors, and will have significant implications for potential treatments of retinal degeneration.